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Genetic determinants and epigenetic effects of pioneer-factor occupancy.
Donaghey, Julie; Thakurela, Sudhir; Charlton, Jocelyn; Chen, Jennifer S; Smith, Zachary D; Gu, Hongcang; Pop, Ramona; Clement, Kendell; Stamenova, Elena K; Karnik, Rahul; Kelley, David R; Gifford, Casey A; Cacchiarelli, Davide; Rinn, John L; Gnirke, Andreas; Ziller, Michael J; Meissner, Alexander.
Afiliação
  • Donaghey J; Broad Institute of MIT and Harvard, Cambridge, MA, USA.
  • Thakurela S; Department of Stem Cell and Regenerative Biology, Harvard University, Cambridge, MA, USA.
  • Charlton J; Broad Institute of MIT and Harvard, Cambridge, MA, USA.
  • Chen JS; Department of Stem Cell and Regenerative Biology, Harvard University, Cambridge, MA, USA.
  • Smith ZD; Department of Stem Cell and Regenerative Biology, Harvard University, Cambridge, MA, USA.
  • Gu H; Department of Genome Regulation, Max Planck Institute for Molecular Genetics, Berlin, Germany.
  • Pop R; Department of Stem Cell and Regenerative Biology, Harvard University, Cambridge, MA, USA.
  • Clement K; Broad Institute of MIT and Harvard, Cambridge, MA, USA.
  • Stamenova EK; Department of Stem Cell and Regenerative Biology, Harvard University, Cambridge, MA, USA.
  • Karnik R; Broad Institute of MIT and Harvard, Cambridge, MA, USA.
  • Kelley DR; Department of Stem Cell and Regenerative Biology, Harvard University, Cambridge, MA, USA.
  • Gifford CA; Broad Institute of MIT and Harvard, Cambridge, MA, USA.
  • Cacchiarelli D; Department of Stem Cell and Regenerative Biology, Harvard University, Cambridge, MA, USA.
  • Rinn JL; Broad Institute of MIT and Harvard, Cambridge, MA, USA.
  • Gnirke A; Broad Institute of MIT and Harvard, Cambridge, MA, USA.
  • Ziller MJ; Department of Stem Cell and Regenerative Biology, Harvard University, Cambridge, MA, USA.
  • Meissner A; Department of Stem Cell and Regenerative Biology, Harvard University, Cambridge, MA, USA.
Nat Genet ; 50(2): 250-258, 2018 02.
Article em En | MEDLINE | ID: mdl-29358654
ABSTRACT
Transcription factors (TFs) direct developmental transitions by binding to target DNA sequences, influencing gene expression and establishing complex gene-regultory networks. To systematically determine the molecular components that enable or constrain TF activity, we investigated the genomic occupancy of FOXA2, GATA4 and OCT4 in several cell types. Despite their classification as pioneer factors, all three TFs exhibit cell-type-specific binding, even when supraphysiologically and ectopically expressed. However, FOXA2 and GATA4 can be distinguished by low enrichment at loci that are highly occupied by these factors in alternative cell types. We find that expression of additional cofactors increases enrichment at a subset of these sites. Finally, FOXA2 occupancy and changes to DNA accessibility can occur in G1-arrested cells, but subsequent loss of DNA methylation requires DNA replication.
Assuntos

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Fatores de Transcrição / DNA / Epigênese Genética / Redes Reguladoras de Genes Limite: Humans Idioma: En Revista: Nat Genet Assunto da revista: GENETICA MEDICA Ano de publicação: 2018 Tipo de documento: Article País de afiliação: Estados Unidos

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Fatores de Transcrição / DNA / Epigênese Genética / Redes Reguladoras de Genes Limite: Humans Idioma: En Revista: Nat Genet Assunto da revista: GENETICA MEDICA Ano de publicação: 2018 Tipo de documento: Article País de afiliação: Estados Unidos